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12/7/2022

CELLULAR PHYSIOLOGY – 2
TRANSPORT ACROSS CELL MEMBRANE

Giảng viên : ThS. BS. Đặng Nguyễn Tường Vân


(dntvan@medvnu.edu.vn)

Bài giảng lý thuyết trực tuyến Khoa Y – ĐHQG HCM |1

Units
• amounts of solute: moles, equivalents, or
osmoles.
• concentrations of solutes: moles per liter
(mol/L), equivalents per liter (Eq/L), or osmoles
per liter (Osm/L) → millimoles per liter
(mmol/L), milliequivalents per liter (mEq/L), or
milliosmoles per liter (mOsm/L)
• 1 mole = 6.022 × 1023 molecules of a
substance. 1 millimole = 1/1000 or 10−3 moles.
• equivalent = the amount of charged (ionized)
solute
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Units
• osmole = no. of particles into which a solute
dissociates in solution.
• Osmolarity = the concentration of particles
in solution = osmoles/L.
• If a solute does not dissociate in solution,
osmolarity = molarity.
• If a solute dissociates in solution, osmolarity
= molarity * no. of particles in solution

ThS. BS. Đặng Nguyễn Tường Vân


Khoa Y – ĐHQG - HCM

Electroneutrality of Body
Fluid Compartments
• Principle of
macroscopic
electroneutrality
• Each compartment:
mEq/L of cations =
mEq/L of anions
• Even when potential
difference across the
cell membrane, charge
balance still is
maintained in the bulk
(macroscopic) solutions

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Composition of ICF and ECF

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Creation of Concentration Differences


across Cell Membranes

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Physiologic function of the


differences in composition
1. The resting membrane potential of nerve and
muscle critically depends on the difference in
concentration of [K+]
2. The upstroke of the action potential of these
same excitable cells depends on the
differences in [Na+]
3. Excitation-contraction coupling in muscle cells
depends on the differences in [Ca2+]
4. Absorption of essential nutrients depends on
the transmembrane [Na+]
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Khoa Y – ĐHQG - HCM

Concentration Differences between


Plasma and ISF
• Plasma has Protein
• Gibbs-Donnan equilibrium: impermeant,
negatively charged proteins in plasma
require electroneutrality → plasma must
have a slightly lower concentration of
small anions (Cl−) and a slightly higher
concentration of small cations (Na+ and
K+) than ISF
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Characteristics of Cell Membranes

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Khoa Y – ĐHQG - HCM

Fluid mosaic model of cell


membranes

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Terms

• Pump
• Transporter
=carrier
• Channel
• Leaking
channel

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Gated channels

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Gating of channels
1. Ligand = requires
binding of specific
CHEMICAl to open
2. Voltage = requires a
specific gradient of
ELECTRICAL CHARGE
across the membrane
to open
3. Mechanical = requires
specific TENSION to
open
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Importance of pumps,
transporters & channels
• Physiology processes:
- growth
- metabolic activities
- sensory
• Diseases:
- defective transporter: cystic fibrosis
- defective channel: long QT syndrome, paralysis
• Pharmacological therapies:
- hypertension: diuretics
- stomach ulcer: proton pump inhibitor
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Transport across Cell


Membranes

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Types of mechanism

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Carrier-mediated transport

• Simple diffusion = not carrier


mediated.
• Facilitated diffusion, primary active
transport, and secondary active
transport = carrier-mediated
transport (involve integral membrane
proteins)

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Khoa Y – ĐHQG - HCM

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Carrier-mediated transport

• 3 characteristics:
1. Saturation:
carrier proteins
have a limited
number of
binding sites for
the solute

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Carrier-mediated transport

• 3 characteristics:
1. Saturation
2. Stereospecificity: binding sites for solute on the
transport proteins are stereospecific.
Ex: the transporter for glucose in the renal proximal
tubule recognizes and transports the natural isomer
D-glucose, but it does not recognize or transport the
unnatural isomer L-glucose

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Carrier-mediated transport

• 3 characteristics:
1. Saturation
2. Stereospecificity
3. Competition: may recognize, bind, and even
transport chemically related solutes
Ex: the transporter for glucose is specific for D-
glucose, but it also recognizes and transports a
closely related sugar, D-galactose → the presence of
D-galactose inhibits the transport of D-glucose by
occupying the sites

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Simple diffusion
• Random thermal
movement of
molecule across a
surface per unit
time
• Net flux is
determined by
gradient: high to
low
• Ex: urea from ECF
to ICF

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Gap junctions

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Net diffusion depends on

1. Concentration gradient (C)


2. Partition coefficient (K):
solubility of a solute in oil
relative to its solubility in water
3. Diffusion coefficient (D)
4. Thickness of the membrane
5. Surface area available for
diffusion

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Facilitated diffusion

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Facilitated diffusion

• Down an electrochemical potential gradient


• no input of metabolic energy
• membrane carrier
• characteristics of carrier-mediated
• GLUT4: D-glucose transport in skeletal
muscle and adipose tissue cells

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Primary active transport


• against an electrochemical potential gradient
(uphill)
• Requires metabolic energy in the form of ATP
• ATP energy source is directly coupled to the
transport process
• Ex: Na+-K+ ATPase in all cell membranes,
Ca2+ ATPase in sarcoplasmic and endoplasmic
reticulum, and H+-K+ATPase in gastric
parietal cells

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Na+-K+ ATPase

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Ca2+ ATPase

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H+-K+ATPase

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Secondary active transport


• the transport of 2 or more solutes is coupled:
one (usually Na+) downhill and other uphill
• metabolic energy
• ATP is supplied indirectly in the Na+
concentration gradient across the cell
membrane (The Na+-K+ ATPase, utilizing ATP,
creates and maintains this Na+ gradient)
• 2 types:
1. Cotransport (symport)
2. Countertransport (antiport, exchange)
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Secondary active transport

• Moves more
than 1 solute
at the same
time

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Cotransport
• Same direction
• Na+-glucose
cotransport
(SGLT) and Na+-
amino acid
cotransport: in
the luminal
membranes of
the epithelial cells
of small intestine
and renal
proximal tubule
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Cotransport
• Na+-K+-
2Cl−
cotransport
in the
luminal
membrane
of epithelial
cells of the
thick
ascending
limb

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Countertransport

• opposite
directions: Na+
into the cell,
solute out of
the cell
• Ca2+-Na+
exchange in
muscle cells

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Countertransport

• Na+-H+
exchange
in renal
proximal
tubules

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Transcellular transporter

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CELLULAR PHYSIOLOGY
OSMOSIS

Giảng viên : ThS. BS. Đặng Nguyễn Tường Vân


(dntvan@medvnu.edu.vn)

Bài giảng lý thuyết trực tuyến Khoa Y – ĐHQG HCM | 37

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Concentration of water

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Osmosis

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Osmosis

• Movement of water
• Only occurs by DIFFUSION
• Aquaporin channel = facilitated diffusion
• Highest concentration in pure water

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Osmosis

• Osmosis = the flow of water across a


semipermeable membrane because of
differences in solute concentration.
• Concentration differences of impermeant
solutes.
• Osmosis ≈ diffusion of water

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Osmotic pressure
 The pressure required to stop the flow of water

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Osmotic pressure
• Depends on
1. the concentration of
osmotically active
particles
2. whether the solute can
cross the membrane or
not
• van’t Hoff equation

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Reflection coefficient (σ)

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Terms

 Isosmotic
 Hypo-
osmotic
 Hyper-
osmotic

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Tonicity and cell membrane

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Tonicity
• 2 solutions separated by a semipermeable
membrane have the same effective osmotic
pressure → isotonic
• 2 solutions have different effective osmotic
pressures, the solution with the lower effective
osmotic pressure is hypotonic and the solution
with the higher effective osmotic pressure is
hypertonic. Water will flow from the hypotonic
solution into the hypertonic solution.

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Cases
Condition Total body ECF volume ICF volume ECF
water osmolarity
IV isotonic increase =
saline (NaCl)
Diarhea decrease =
(isotonic loss)
Excessive = Increase
NaCl intake
Excessive Decrease Increase
sweating
(hypotonic
loss)

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